The mevalonate pathway has been extensively used to produce a range of valuable chemicals via isopentenyl pyrophosphates (IPP) or dimethylallyl pyrophosphates (DMAPP) as essential intermediates for terpene synthesis. In addition to terpene-based chemicals, Chou and colleagues engineered the mevalonate pathway in Escherichia coli to produce isopentenols via hydrolysis of IPP to 3-methyl-3-butenol (Chou and Keasling, Appl. Environ. Microbiol. 2012). In this pathway, 3 ATPs are required to produce one molecule of IPP from one molecule of mevalonate. Among these 3 ATPs, two ATPs are consumed for two-step phosphorylations to produce mevalonate pyrophosphate, but the pyrophosphate group is subsequently hydrolyzed to produce isopentenol from IPP. As a result, the overall pathway is not only energetically demanding but also inefficient because of unnecessary phosphorylation-dephosphorylation steps. Furthermore, the energy and cost demand of this pathway has been a problem, especially when a production in large scale using fermentor is exploited since it requires extensive aeration to facilitate ATP generation in E. coli. 
To our knowledge, there has been no report that attempts to resolve the aforementioned problem in the mevalonate-derived isopentenol pathway. Although there were other pathways reported to produce isopentenols of which carbon backbones were derived from keto acids intermediates in biosynthesis pathways of valine, leucine and isoleucine (Atsumi et al. Nature 2008). However, biosynthesis of these amino acids from pyruvate requires multiple biochemical reactions, which are tightly regulated in E. coli. In addition, to produce isopentenols from these keto acids precursors, two more enzymes (keto acids decarboxylase and alcohol dehydrogenase) are required. Given of E. coli strains and pathways that produce mevalonate in a high titer, we hope to invent a new pathway that lower down the energy cost per isopentenol synthesis from mevalonate by bypassing the phosphorylation reactions performed by mevalonate kinase (MK) and phosphomevalonate kinase (PMK) towards a more cost-effective biological system.